Volume 40 Supplement 1

70th Congress of the Italian Society of Pediatrics

Open Access

Metabolomics in the diagnosis of sepsis

  • Vassilios Fanos1,
  • Mauro Stronati2,
  • Diego Gazzolo3 and
  • Giovanni Corsello4
Italian Journal of Pediatrics201440(Suppl 1):A11

https://doi.org/10.1186/1824-7288-40-S1-A11

Published: 11 August 2014

Introduction

Sepsis is an important cause of mortality and morbidity for preterm and hospitalized newborn babies. Today, no single test satisfies the criteria as being the ideal marker for the early diagnosis of neonatal sepsis. Analysis of the entire metabolome is a promising method for determining metabolic variations correlated with sepsis [16].

Metabolomics profiling and sepsis

Works on metabolomics concerning sepsis conducted on animals and humans of different ages (newborn and adults) have recently been published and are presented in Table 1. In septic patients compared to controls (in plasma and urine) it is possible to observe an increase of metabolites which are part of the oxidative metabolism of fatty acids (such as hydroxybutyrate, acylcarnitines and acetoacetate). Briefly stated, alterations in the glucose metabolism in critical conditions can be seen as a redistribution of glucose consumption from the mitochondrial oxidative phosphorylation to other metabolic pathways, such as the production of lactate and the pentose phosphate pathway. In the study by Fanos et al. [7] a combined approach based on both nuclear magnetic resonance (1)H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques was used applied to neonatal infections. The study population included 25 neonates: 9 patients had a diagnosis of sepsis and 16 were healthy controls. This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05). Mickiewicz et al [8] examined serum samples collected from 60 patients with septic shock (by Gram- and/or Gram+), 40 patients with SIRS and 40 healthy children by nuclear magnetic resonance spectroscopy spectra. Some of the metabolite concentrations were able to separate between patient groups. The main messages from the published studies are as follows. a) Metabolomics is able to early diagnose the infection (in some cases in preclinical conditions). b) Metabolomics is able to predict the outcome in single individuals and the AUC values are close to 1. c) Metabolomics appears to be a promising and useful instrument also in the diagnosis of sepsis. d) In the next future some easy tools, like urinary dipsticks, with the discriminant metabolites will be available in clinical settings, bedside.
Table 1

Metabolomic studies that have analyzed the metabolic profiles of septic patients and of experimental animals (From ref. 6, mod.)

Author

Population study

Sample

Metabolomic analysis

Metabolite alterations

Fanos et al. 2014

9 septic newborns vs 16 control newborns

Urine

GC-MS

1H NMR

Lactate, glucose, maltose, ribitol, ribonic acid, pseudo-uridine, 2,3,4 trihydroxybutiric acid, 2-ketpgluconic acid, 3,4 hydroxybutanoic acid, 3,4,5 trihydroxypentanoic acid <(GC-MS)

Acetate, acetone, citrate, creatinine, glycine, lactate, lysine, glucose (1H-NMR)

Mickiewicz et al. 2013

60 septic shock vs 40 SIRS vs 40 control pediatric patients

Serum

1H-NMR

2-hydroxybutyrate, 2-hydroxyisovalerate, lactate, glucose, 2-oxoisocaproate, creatine, creatinine, histidine, and phenylalanine

Schmerler et al. 2012

74 SIRS vs 69 septic vs 16 control human adults

Blood

LC-MS/MS

Acylcarnitines and glycerophosphatidylcholines

Mickiewitz et al. 2014

39 septic shock adult patients vs 20 ICU control patients

Serum

1H-NMR

Isobutyrate, phenylalanine, 2 hydroxyisovalerate, myoinositol, acetylcarnitine, creatine, lactate, valine, arginine, methanol, glucose, glycine

Liu et al. 2010

40 septic vs control rats

Plasma

UPLC–Q-TOF-MS

Hypoxanthine, indoxyl sulfate, glucuronic acid, gluconic acid, proline, uracil, nitrotyrosine, uric acid and trihydroxy cholanoic acid

Lin et al. 2009

40 septic vs 20 control rats

Serum

1H NMR

Lactate, alanine, acetate, acetoacetate, hydroxybutyrate and formate

Izquierdo-Garcìa et al. 2011

14 septic vs 14 control rats

Lung tissue, BALF and serum

1H NMR

Alanine, creatine, phosphoethanolamine and myoinositol

Conclusions

Present-day methods and procedures for the diagnosis of systemic neonatal infections are hindered by low sensitivity and long response times. Metabolomics is showing promise of becoming a most effective method, even in neonatology and paediatrics.

Authors’ Affiliations

(1)
Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, University of Cagliari
(2)
Neonatal Unit and Neonatal Intensive Care Unit, Maternal-Infant Department, Fondazione IRCCS Policlinico San Matteo
(3)
Department of Maternal, Fetal and Neonatal Health, C. Arrigo Children's Hospital
(4)
Operative Unit of Pediatrics and Neonatal Intensive Therapy, Mother and Child Department, University of Palermo

References

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Copyright

© Fanos et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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